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Open Access Research

Autophagy involved in lipopolysaccharide-induced foam cell formation is mediated by adipose differentiation-related protein

Xuyang Feng1, Yuan Yuan2, Chao Wang2, Jun Feng3, Zuyi Yuan4, Xiumin Zhang2, Wen Sui2, Peizhen Hu2, Pengfei Zheng2 and Jing Ye2*

Author Affiliations

1 Department of cardiology, Xijing Hospital, The Fourth Military Medical University, Xi’an 710032, China

2 Department of Pathology, Xijing Hospital, The Fourth Military Medical University, Xi’an 710032, China

3 Department of Cerebral vessels, First Affiliated Hospital of Medical College, Xi’an Jiaotong University, Xi’an 710061, China

4 Department of cardiology, First Affiliated Hospital of Medical College, Xi’an Jiaotong University, Xi’an 710061, China

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Lipids in Health and Disease 2014, 13:10  doi:10.1186/1476-511X-13-10

Published: 9 January 2014

Abstract

Background

Autophagy is an essential process for breaking down macromolecules and aged/damaged cellular organelles to maintain cellular energy balance and cellular nutritional status. The idea that autophagy regulates lipid metabolism is an emerging concept with important implications for atherosclerosis. However, the potential role of autophagy and its relationship with lipid metabolism in foam cell formation remains unclear. In this study, we found that autophagy was involved in the lipopolysaccharide (LPS)-induced the formation of foam cells and was at least partially dependent on adipose differentiation-related protein (ADRP).

Method

Foam cell formation was evaluated by Oil red O staining. Autophagic activity was determined by immunofluorescence and Western blotting. ADRP gene expression of ADRP was examined by real-time PCR (RT-PCR). The protein expression of ADRP and LC3 was measured using Western blotting analysis. Intracellular cholesterol and triglyceride levels in foam cells were quantitatively measured by enzymatic colorimetric assays.

Results

LPS promoted foam cell formation by inducing lipid accumulation in macrophages. The activation of autophagy with rapamycin (Rap) decreased intracellular cholesterol and triglyceride levels, whereas the inhibition of autophagy with 3-methyladenine (3MA) enhanced the accumulation of lipid droplets. Overexpression of ADRP alone increased the formation of foam cells and consequently autophagic activity. In contrast, the inhibitory effects of ADRP activity with siRNA suppressed the activation of autophagy. Taken together, we propose a novel role for ADRP in the regulation of macrophage autophagy during LPS stimulation.

Conclusion

We defined a new molecular pathway in which LPS-induced foam cell formation is regulated through autophagy. These findings facilitate the understanding of the role of autophagy in the development of atherosclerosis.

Keywords:
Lipopolysaccharide; Lipid droplet; Foam cell; Autophagy; ADRP